Kalata B1 and Kalata B2 Have a Surfactant-Like Activity in Phosphatidylethanolomine-Containing Lipid Membranes
Kalata B1 and Kalata B2 Have a Surfactant-Like Activity in Phosphatidylethanolomine-Containing Lipid Membranes
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DOI：
10.1021/acs.langmuir.7b01642
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发表时间：
2017-07-04
期刊：
影响因子：
3.9
通讯作者：
Cornell, Bruce
中科院分区：
文献类型：
--
作者：
Cranfield, Charles G.;Henriques, Sonia Troeira;Cornell, Bruce
环肽是富含二硫键的环状肽，具有化学和热稳定性，并具有药物和杀虫特性。报道的环肽的活性与其靶向磷脂酰乙醇胺（PE）-磷脂和破坏细胞膜的能力相关。然而，这种破坏发生的机制仍不清楚。在目前的研究中，我们研究的原型cyclotides，kalata B1（KB 1）和kalata B2（KB 2），栓系的脂质双层膜（tBLMs），使用扫频电阻抗谱的效果。我们证实，kB 1和kB 2结合的双层，只有当它们含有PE-磷脂。我们推测，在添加kB 1或kB 2后观察到的膜传导和电容的增加不太可能是由离子通道样孔引起的，但与螺旋环形孔的形成一致。这一假设得到了kB 1和kB 2效应的浓度依赖性的支持，这表明临界胶束浓度事件，而不是由增加的通道插入引起的传导的逐渐增加。另外，当肽从双层冲洗时，传导行为是容易可逆的。我们的研究结果支持一种机制，其中kB 1和kB 2绑定到并破坏含PE的膜，通过降低整体膜的关键包装参数，将表面活性剂，然后打开或增加现有的膜缺陷的大小。环肽类化合物不需要直接参与导电孔，但可能通过改变膜填充约束和诱导纯疏水性导电孔来间接发挥其作用。
Cyclotides are cyclic disulfide-rich peptides that are chemically and thermally stable and possess pharmaceutical and insecticidal properties. The activities reported for cyclotides correlate with their ability to target phosphatidylethanolamine (PE)-phospholipids and disrupt cell membranes. However, the mechanism by which this disruption occurs remains unclear. In the current study we examine the effect of the prototypic cyclotides, kalata B1 (kB1) and kalata B2 (kB2), on tethered lipid bilayer membranes (tBLMs) using swept frequency electrical impedance spectroscopy. We confirmed that kB1 and kB2 bind to bilayers only if they contain PE-phospholipids. We hypothesize that the increase in membrane conduction and capacitance observed upon addition of kB1 or kB2 is unlikely to result from ion channel like pores but is consistent with the formation of lipidic toroidal pores. This hypothesis is supported by the concentration dependence of effects of kB1 and kB2 being suggestive of a critical micelle concentration event rather than a progressive increase in conduction arising from increased channel insertion. Additionally, conduction behavior is readily reversible when the peptide is rinsed from the bilayer. Our results support a mechanism by which kB1 and kB2 bind to and disrupt PE-containing membranes by decreasing the overall membrane critical packing parameter, as would a surfactant, which then opens or increases the size of existing membrane defects. The cyclotides need not participate directly in the conductive pore but might exert their effect indirectly through altering membrane packing constraints and inducing purely lipidic conductive pores.